Literature summary for 3.5.1.18 extracted from

Dutta, D.; Mishra, S.
Loss of catalytic activity in the E134D, H67A, and H349A mutants of DapE mechanistic analysis with QM/MM investigation (2016), J. Phys. Chem. B, 120, 11654-11664 .

Search for more literature for 3.5.1.18

Application

Application	Comment	Organism
medicine	inhibition of the catalytic action of the microbial enzyme DapE is fatal to the growth of bacteria and critical to the use of this enzyme as a potential antibiotic target	Haemophilus influenzae

Protein Variants

Protein Variants	Comment	Organism
E134D	the free energy of substrate binding in the mutant enzyme is compared with the substrate binding free energy in the wild-type enzyme. In the case of E134D mutation, the shorter side chain length of the Asp residue at the 134 position (compared to Glu134 in the wild-type enzyme) makes the negatively charged carboxylate group of the Asp134 residue more distant from the negatively charged substrate, N-succinyl-LL-2,6-diaminoheptanedioate. In addition, the metal centers contribute more favorably toward the substrate binding in the E134D mutant as compared to that in wild-type enzyme, which indicates a stronger substrate binding with the metal centers in the mutant. The increased metal-substrate binding in the E134D mutant is a result of the shorter side chain of Asp134, which allows the negatively charged N-succinyl-LL-2,6-diaminoheptanedioate to come closer to the metal centers in E134D as compared to that in wild-type enzyme	Haemophilus influenzae
H349A	the free energy of substrate binding in the mutant enzyme is compared with the substrate binding free energy in the wild-type enzyme. Compared to wild-type enzyme, a relatively weaker substrate binding is observed in the histidine mutant Compared to wild-type enzyme, a relatively weaker substrate binding is observed in the histidine mutant. The computed values of the free energy of substrate binding in this study suggest no substrate binding in the H349A mutant	Haemophilus influenzae
H67A	the free energy of substrate binding in the mutant enzyme is compared with the substrate binding free energy in the wild-type enzyme. Compared to wild-type enzyme, a relatively weaker substrate binding is observed in the histidine mutant. The computed values of the free energy of substrate binding in this study suggest a less favorable substrate binding in the H67A mutant compared to wild-type enzyme	Haemophilus influenzae
H67A/H349A	the proton transfer process is not possible in the mutant, the catalytic activities are effectively quenched (as determined by relaxed potential energy scan)	Haemophilus influenzae

Metals/Ions

Metals/Ions	Comment	Organism	Structure
Zn2+	two Zn metal centers are essential to the catalytic action of the DapE enzyme. His67, His349, and Glu134 residues in the active site	Haemophilus influenzae

Organism

Organism	UniProt	Comment	Textmining
Haemophilus influenzae	P44514	-	-
Haemophilus influenzae ATCC 51907	P44514	-	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
N-succinyl-LL-2,6-diaminoheptanedioate + H2O	a combination of different computational methods, such as protein-ligand docking, MD simulations, free-energy analysis with the MM-PBSA method, and hybrid QM/MM calculations, to provide a detailed account of the substrate binding and catalytic reaction in three important mutants of DapE and compared them to the action of the wt-DapE	Haemophilus influenzae	succinate + LL-2,6-diaminoheptanedioate	-	?
N-succinyl-LL-2,6-diaminoheptanedioate + H2O	a combination of different computational methods, such as protein-ligand docking, MD simulations, free-energy analysis with the MM-PBSA method, and hybrid QM/MM calculations, to provide a detailed account of the substrate binding and catalytic reaction in three important mutants of DapE and compared them to the action of the wt-DapE	Haemophilus influenzae ATCC 51907	succinate + LL-2,6-diaminoheptanedioate	-	?

Synonyms

Synonyms	Comment	Organism
DapE	-	Haemophilus influenzae

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Release 2023.1 (January 2023)